Are You Confident of the Diagnosis?

What you should be alert for in the history

The term sebaceoma was introduced in 1984 by Troy and Ackerman to describe a benign adnexal tumor differentiating toward sebocytes, distinct from sebaceous hyperplasia, sebaceous adenoma, basal cell carcinoma with sebaceous differentiation and sebaceous carcinoma. Sebaceoma was meant to redefine the previously used and confusing term “sebaceous epithelioma,” which was not well defined in the literature.

Characteristic findings on physical examination

Lesions typically occur on the face and scalp, although cases on the chest, back and neck have been described. Sebaceoma can arise in a pre-existing nevus sebaceus. Clinically sebaceomas are typically solitary, yellow-orange papules or nodules that range in size from 6 mm up to 3 cm in diameter.

Recognition of this tumor is important as it can be associated with Muir-Torre Syndrome (MTS). Although sebaceous adenoma is the most common sebaceous lesion associated with this syndrome, sebaceoma can also occur, either as a solitary or multiple lesions. MTS is an autosomal dominant condition associated with visceral malignancy.

Expected results of diagnostic studies

Histologically sebaceomas are lobulated basaloid tumors, often with epidermal contiguity. The low power profile is that of a well circumscribed, symmetrical lesion with smooth borders, located in the upper dermis (Figure 1, Figure 2). By definition the basaloid component comprises greater than 50% of the tumor. This is important in distinguishing sebaceoma from sebaceous adenoma in which basaloid cells represent less than 50% of the tumor.

Figure 1.

Low power view of a sebaceoma. It is a well circumscribed, symmetrical basaloid tumor containing scattered sebocytes. There is no atypia, increased mitotic activity or tumor necrosis (H&E).

Figure 2.

The sebaceous component of the lesion does not form lobules or glands; rather sebocytes are scattered in a random distribution. Sebocytes are characterized by a foamy, vacuolated cytoplasm and round to oval nuclei with scalloped borders. Basloid cells are monomorphous with small, round nuclei without prominent nucleoli. Cytologic atypia is not present and mitoses are few and morphologically typical.

Holocine degeneration may be seen in areas with more numerous sebocytes but there is no tumor necrosis. Ducts and cystic areas are common. Ducts are lined by an eosinophilic cuticle. The surrounding stroma is dense and eosinophilic. Clefting between tumor and stroma is not a feature, and peripheral palisading of basaloid cells is not seen. Focal calcification can occur.

Variants of sebaceoma include rippled-pattern sebaceoma. This lesion is characterized by foci of cigar-shaped basaloid cells arranged in linear, parallel rows similar to Verocay bodies in schwannoma. A reticulated and cribiform sebaceoma has also been reported. The verruca/seborrheic keratosis type of sebaceoma is rare. This lesion connects to the overlying follicular infundibula, which demonstrates features of a wart or seborrheic keratosis.

Sebaceomas that arise within a nevus sebaceus will occur in a background of epidermal papillomatosis with increased numbers of sebaceous lobules underlying the epidermis and an increased number of apocrine glands in the deep dermis/subcutaneous fat, features typical of a nevus sebaceus.

Immunohistochemical stains are available to look for loss of mismatch repair proteins in paraffin-embedded tissue: MSH-2, MLH-1, MSH-6. Loss of expression of these proteins is associated with MTS. Initial studies examined expression of MLH-1 and MSH-2. More recently, loss of MSH-6 has also been demonstrated in patients with MTS. The positive predictive value for a diagnosis of MTS when combining these three markers ranges from 55% to 100%.

Diagnosis confirmation

The differential diagnosis of sebaceoma includes sebaceous adenoma. Although there may be considerable overlap between these two entities, when basaloid cells comprise more than half of the tumor, sebaceoma is favored. Trichoblastomas with sebaceous differentiation may also be challenging to distinguish from sebaceoma. The former is characterized by the presence of follicular differentiation, namely, follicular germs and foci of peripheral palisading.

Another lesion on the differential diagnosis of sebaceoma is poroma with sebaceous differentiation. This lesion contains tubular structures and poroid cells. Basal cell carcinoma with sebcaeous differentiation is fundamentally a basal cell carincoma which has foci of mature sebocytes within tumor lobules. The presence of peripheral palisading of a predominantly basaloid tumor with retraction artifact separating the tumor lobule from the adjacent stroma, and a loose mucinous stroma are clues to a basal cell carcinoma.

CK 19 positivity has been reported as a helpful tool in differentiating basal cell carcinoma from sebaceous tumors. Strong CK 19 positivity supports a diagnosis of basal cell carcinoma. Another immunohistochemical panel that can aid in distinguishing basal cell carcinoma from sebaceoma is Ber-EP4 and EMA. Sebaceomas are Ber-EP4 negative, EMA positive in sebaceous areas and basal cell carcinoma is Ber-EP4 positive and EMA negative.

Sebaceous carcinoma is distinguished from sebaceoma by its lack of circumscription and symmetry and the presence of cytologic atypia, pleomorphism with vesicular nuclei and prominent nucleoli and presence of mitoses and tumor necrosis.

Who is at Risk for Developing this Disease?

Sebaceoma is more common in females. The age of affected patients ranges from 22 to 87 years with the majority of cases occurring in those over the age of 50 years.

Sebaceoma is usually sporadic but can be a marker for Muir-Torre syndrome (MTS). MTS is an autosomal dominant defect in DNA mis-match repair associated with multiple sebaceous tumors, keratoacanthomas and internal malignancy. It demonstrates a slight male predominance (male:female ratio 3:2). The median age at presentation of the first malignancy is 53 years.

What is the Cause of the Disease?

Etiology

Pathophysiology

The cause for sporadic sebaceomas is unknown.

Cases associated with Muir-Torre syndrome are due to a defect in DNA mismatch repair proteins. The best studied genes are MSH-2 on chromosome 2, which is most common, and MLH-1 on chromosome 3. Other implicated genes include MSH-6 and MLH-3. These proteins function to repair mismatches in DNA. Mutations lead to microsatellite instability and tumors. Microsatellite instablity is also seen in hereditary non-polyposis colorectal cancer, and MTS may be a variant of those disorders.

Systemic Implications and Complications

Patients with Muir-Torre syndrome (MTS) are at risk for visceral malignancy. Of the visceral malignancies, colorectal carcinoma is most common. Genitourinary, breast, upper gatrointestinal, laryngeal, and hematologic malignancies have also been reported. Although the visceral neoplams in MTS may have a less aggressive course compared with sporadic counterparts, 60% of patients with MTS develop metastatic disease. Half of all patients have two or more internal malignancies. 56% of cutaneous lesions are diagnosed after the internal malignancy; 22% of cutaneous lesions occur before the internal malignancy and 6% are concomitant.

Treatment Options

Lesions are benign and conservative surgical excision is curative. There are no reports of recurrence or metastasis.

Optimal Therapeutic Approach for this Disease

Conservative surgical excision is curative. There are no reports of recurrence or metastasis.

Patient Management

Evaluation for Muir Torre Syndrome (MTS) is important and can be done with immunohistochemical stains and patient history. Patients with MTS should undergo close cancer surveillance and assessment of family members. Genetic testing on peripheral blood is also available to confirm microsatellite instability.

Unusual Clinical Scenarios to Consider in Patient Management

There are rare reports of sebaceoma in the external auditory canal. A sebaceoma arising in association with a seborrheic keratosis as a contiguous but distinct tumor is also reported.

What is the Evidence?

(The original paper in which Troy and Ackerman introduce the term sebaceoma to “supersede, not merely to redefine, what has been previously called sebaceous epithelioma.” 14 cases of the entity are presented with detailed clinical and pathologic descriptions.)

(Misago’s group reviews 30 basaloid tumors with sebaceous differentiation and classifies them into 6 groups: sebaceoma, trichoblastoma with sebaceous differentiation, poroma with sebaceous differentiation, low-grade sebaceous carcinoma, sebaceous carcinoma and basal cell carcinoma. They subclassify sebaceoma into classic and verrucous/seborrheic keratosis types. Clinical data are provided and there is a detailed pathologic analysis of each category of tumor.)

(The authors review the significance and role of immunohistochemical stains for microsatellite instablility in the diagnosis of MTS and propose an algorithm for histopathologic diagnosis of possible MTS in sebaceous tumors of the skin.)

(This review article describes the epidemiology, clinical features and molecular biology of Muir Torre Syndrome. It explores the relationship of MTS to Lynch syndrome and details the management and appropriate follow-up of persons with MTS.)

(This describes sebaceoma in the external auditory canal of a 73-year-old woman. It was a slowly growing 2 x 1.5 cm plaque, present for a few months and without headaches, vertigo or association with Muir-Torre syndrome.)